..MicroRNAs (miRNAs) comprise a family of short non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. Rapidly growing evidence indicates that miRNAs play a key role in drug (xenobiotic) metabolism...

Epigenetic aspects of genotoxic and non-genotoxic hepatocarcinogenesis: studies in rodents

..This review presents evidence suggesting the involvement of DNA hypomethylation in the pathogenesis of several major human pathologies, including cancer, atherosclerosis, Alzheimer's disease, and psychiatric disorders...

..Together, these data suggest that the proper maintenance of the epigenomic landscape in normal brain depends on the adequate supply of essential nutrients involved in the metabolism of methyl groups...

Role of DNA damage and alterations in cytosine DNA methylation in rat liver carcinogenesis induced by a methyl-deficient diet

..None of the samples exhibited coding region mutations. Given that p53 mutations are rare in primary human liver tumors, these data suggest that transcriptional repression by p53 promoter methylation may contribute to tumor progression...

..These data indicate the importance of epigenetic alterations in the mechanism of action of peroxisome proliferators and the key role of Pparalpha...

Epigenetic downregulation of the suppressor of cytokine signaling 1 (Socs1) gene is associated with the STAT3 activation and development of hepatocellular carcinoma induced by methyl-deficiency in rats

..This model illustrates that the Socs1 acts as classic tumor suppressor by preventing activation of the STAT3 and downregulation of Socs1 and consequent activation of STAT3 may be a crucial events leading to formation of HCC...

De novo methylation of the p16INK4A gene in early preneoplastic liver and tumors induced by folate/methyl deficiency in rats

..In conclusion, we have demonstrated that exposure of rats to genotoxic hepatocarcinogen 2-AAF, in addition to formation of 2-AAF-specific DNA lesions, resulted in substantial alterations in cellular epigenetic status...

Analysis of mutations in the K-ras and p53 genes of lung tumors and in the hprt gene of 6-thioguanine-resistant T-lymphocytes from rats treated with 1,6-dinitropyrene

..In conclusion, we demonstrate that epigenetic alterations precede formation of preneoplastic lesions indicating the significance of epigenetic events in induction of oncogenic pathways in early stages of carcinogenesis...

Abnormal folate metabolism and mutation in the methylenetetrahydrofolate reductase gene may be maternal risk factors for Down syndrome

..These insights in an experimental model are consistent with the possibility that DNA lesions may be a necessary prerequisite for the disruption of normal DNA methylation patterns in preneoplastic and neoplastic cells...

..The results of this study show that deregulation of cellular epigenetic processes plays a crucial role in the mechanism of E(2)-induced mammary carcinogenesis in ACI rats, especially in the tumor initiation process...

..As an increase in tumor numbers was observed only in folate- and choline-deficient mice with low levels of SAM and DNA hypomethylation, the modulatory role of folate may be dependent on the transformation state of the cell...

Germ-line mutations, DNA damage, and global hypermethylation in mice exposed to particulate air pollution in an urban/industrial location

..These data are the first indication that EndoG may be regulated by methylation of its gene promoter, and partially by histone acetylation, and that EndoG is essential for prostate cancer cell death in the used models...

Role of epigenetic effectors in maintenance of the long-term persistent bystander effect in spleen in vivo